ILC1 drive intestinal epithelial and matrix remodelling.

Autor: Jowett GM; Centre for Craniofacial and Regenerative Biology, King's College London, London, UK.; Centre for Host Microbiome Interactions, King's College London, London, UK.; Wellcome Trust Cell Therapies and Regenerative Medicine PhD Programme, London, UK.; Centre for Stem Cells & Regenerative Medicine, King's College London, London, UK., Norman MDA; Centre for Craniofacial and Regenerative Biology, King's College London, London, UK., Yu TTL; Centre for Craniofacial and Regenerative Biology, King's College London, London, UK., Rosell Arévalo P; Centre for Host Microbiome Interactions, King's College London, London, UK., Hoogland D; Department of Chemistry, King's College London, London, UK., Lust ST; Centre for Craniofacial and Regenerative Biology, King's College London, London, UK., Read E; Centre for Host Microbiome Interactions, King's College London, London, UK.; Wellcome Trust Cell Therapies and Regenerative Medicine PhD Programme, London, UK., Hamrud E; Centre for Craniofacial and Regenerative Biology, King's College London, London, UK.; Wellcome Trust Cell Therapies and Regenerative Medicine PhD Programme, London, UK.; Centre for Stem Cells & Regenerative Medicine, King's College London, London, UK., Walters NJ; BioMediTech, Tampere University Tampere Finland, Helsinki, Finland.; Natural Resources Institute Finland, Helsinki, Finland., Niazi U; Guy's and St Thomas' National Health Service Foundation Trust and King's College London National Institute for Health Research Biomedical Research Centre Translational Bioinformatics Platform, Guy's Hospital, London, UK., Chung MWH; Centre for Host Microbiome Interactions, King's College London, London, UK.; Wellcome Trust Cell Therapies and Regenerative Medicine PhD Programme, London, UK.; Centre for Stem Cells & Regenerative Medicine, King's College London, London, UK., Marciano D; Centre for Craniofacial and Regenerative Biology, King's College London, London, UK., Omer OS; School of Immunology and Microbial Sciences, King's College London, London, UK.; Department of Gastroenterology, Guy's and St Thomas' Hospitals NHS Trust, London, UK., Zabinski T; Centre for Host Microbiome Interactions, King's College London, London, UK., Danovi D; Centre for Stem Cells & Regenerative Medicine, King's College London, London, UK., Lord GM; Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Hilborn J; Department of Chemistry, Ångström Laboratory, Uppsala University, Uppsala, Sweden., Evans ND; Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Human Development and Health, Institute of Developmental Sciences, University of Southampton, Southampton, UK., Dreiss CA; Institute of Pharmaceutical Science, King's College London, London, UK., Bozec L; Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada., Oommen OP; Bioengineering and Nanomedicine Lab, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland., Lorenz CD; Department of Physics, King's College London, London, UK., da Silva RMP; Centre for Craniofacial and Regenerative Biology, King's College London, London, UK.; i3S-Instituto de Investigação e Inovação em Saúde-and INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal., Neves JF; Centre for Host Microbiome Interactions, King's College London, London, UK. joana.pereira_das_neves@kcl.ac.uk., Gentleman E; Centre for Craniofacial and Regenerative Biology, King's College London, London, UK. eileen.gentleman@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nature materials [Nat Mater] 2021 Feb; Vol. 20 (2), pp. 250-259. Date of Electronic Publication: 2020 Sep 07.
DOI: 10.1038/s41563-020-0783-8
Abstrakt: Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6 + epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.
Databáze: MEDLINE
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